A Plasmodium Gene Family Encoding Maurer's Cleft Membrane Proteins: Structural Properties and Expression Profiling

Abstract

Upon invasion of the erythrocyte cell, the malaria parasite remodels its environment; in particular, it establishes a complex membrane network, which connects the parasitophorous vacuole to the host plasma membrane and is involved in protein transport and trafficking. We have identified a novel subtelomeric gene family in Plasmodium falciparum that encodes 11 transmembrane proteins localized to the Maurer's clefts. Using coimmunoprecipitation and shotgun proteomics, we were able to enrich specifically for these proteins and detect distinct peptides, allowing us to conclude that four to 10 products were present at a given time. Nearly all of the Pfmc-2tm genes are transcribed during the trophozoite stage; this narrow time frame of transcription overlaps with the specific stevor and rif genes that are differentially expressed during the erythrocyte cycle. The description of the structural properties of the proteins led us to manually reannotate published sequences, and to detect potentially homologous gene families in both P. falciparum and Plasmodium yoelii yoelii, where no orthologs were predicted uniquely based on sequence similarity. These basic proteins with two transmembrane domains belong to a larger superfamily, which includes STEVORs and RIFINs

Molecular and functional aspects of parasite invasion

“…Although the protein and lipid composition of the vacuole membrane is largely uncharacterized, host-derived proteins are noticeably excluded [5] and the content of rhoptries appears to be important in forming the vacuole during invasion. The malaria parasite elaborates a tubulovesicular network that can protrude into the erythrocyte cytoplasm and these extensions may be important for transport of solutes [6]. Other membranous structures such as Maurer's clefts are formed in the host cell cytoplasm and are important in protein trafficking [7].…”

Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle

“…Nine genes uniquely detected here at the transcriptome level were recently highlighted as potential secreted proteins (pPIESPs) in the targeted proteomic analysis of erythrocyte surface proteins . Two other genes (PFC1080c and PF11_0014) encode Maurer's cleft transmembrane proteins, (annotated as PfMC_2TMs), which were detected in the proteomic analysis of coimmunoprecipitated complexes (Sam-Yellowe et al 2004). …”

Protein trafficking in Plasmodium falciparum-infected red cells and impact of the expansion of exported protein families

“…Other parasite-encoded proteins involved in PfEMP-1 trafficking to the surface of infected erythrocytes have been reviewed by Sam-Yellowe (2009). Further investigations are required in order to fully understand the mechanisms behind the transport of proteins beyond the PVM to their final destination in the host-cell cytoplasm and on to the RBC surface.…”